DUSP4 modulates RIG-I- and STING-mediated IRF3-type I IFN response

作者：Huipeng Jiao, Sharmy J. James, Chin Wen Png, Chaoyu Cui, Heng Li, Liang Li, Wan Ni Chia, Nyo Min, Weiyun Li, Carla Claser, Laurent Rénia, Hongyan Wang, Mark Chen, Justin Jang Hann Chu, Kevin S. W. Tan, Yinyue Deng, Yongliang Zhang · 发表于：Cell Death and Differentiation · 年份：2024 · DOI：10.1038/s41418-024-01269-7 · 被引用次数：17 · 研究领域：interferon and immune responses、Inflammasome and immune disorders、Viral Infections and Vectors

Detection of cytosolic nucleic acids by pattern recognition receptors, including STING and RIG-I, leads to the activation of multiple signalling pathways that culminate in the production of type I interferons (IFNs) which are vital for host survival during virus infection. In addition to protective immune modulatory functions, type I IFNs are also associated with autoimmune diseases. Hence, it is important to elucidate the mechanisms that govern their expression. In this study, we identified a critical regulatory function of the DUSP4 phosphatase in innate immune signalling. We found that DUSP4 regulates the activation of TBK1 and ERK1/2 in a signalling complex containing DUSP4, TBK1, ERK1/2 and IRF3 to regulate the production of type I IFNs. Mice deficient in DUSP4 were more resistant to infections by both RNA and DNA viruses but more susceptible to malaria parasites. Therefore, our study establishes DUSP4 as a regulator of nucleic acid sensor signalling and sheds light on an important facet of the type I IFN regulatory system.